GO:0140672 ATAC complex: Components, Assembly and Research Methods

The ATAC complex (GO:0140672) is a multi-subunit chromatin remodeling complex that regulates transcription via acetylation primarily of nucleosomal histones H3 and possibly H4. It shares the histone acetylation (HAT) module of GCN5/PCAF-ADA2-ADA3-SGF29 (or orthologs) with the related SAGA complex (GO:0000124), but contains HAT subunits GCN5 or PCAF in a mutually exclusive manner. In addition to the HAT module, the ATAC complex contains DR1/NC2B, KAT14, MBIP, WDR5, YEATS2 and ZZZ3 or orthologs. The complex also regulates the activity of non-histone targets and orchestrates mitotic progression by regulating Cyclin A degradation through acetylation. Researchers study the ATAC complex because it sits at the interface of chromatin modification, transcription regulation, and cell-cycle control. Its ability to acetylate both histones and non-histone proteins places it in a central position in gene expression programs. Recent work has shown that the ATAC complex represses the transcriptional program of the autophagy-lysosome pathway via its E3 ubiquitin ligase activity, revealing an unexpected link between chromatin regulation and autophagy. Complex-specific inhibitors for interrogating ATAC histone acetyltransferase complex have also been developed, providing new tools to dissect its functions. Understanding the ATAC complex is relevant to human disease because epigenetic dysregulation is increasingly recognized in conditions such as Alzheimer's disease and because chromatin accessibility mapping has become a standard approach to study regulatory landscapes in complex diseases [1,3]. Single-cell atlases of chromatin accessibility in the human genome and spatial multiomic studies of human placenta provide context for how ATAC complex activity shapes cell-type-specific gene regulation. Mapping enhancer-gene regulatory interactions from single-cell data and multimodal chromatin profiling using nanobody-based single-cell CUT&Tag further enable researchers to connect ATAC complex function to regulatory networks.

The ATAC complex (GO:0140672) is a chromatin remodeling complex that regulates transcription via acetylation primarily of nucleosomal histones H3 and possibly H4. It shares the histone acetylation (HAT) module of GCN5/PCAF-ADA2-ADA3-SGF29 (or orthologs) with the related SAGA complex (GO:0000124). The complex contains HAT subunits GCN5 or PCAF in a mutually exclusive manner. In addition to the HAT module, it contains DR1/NC2B, KAT14, MBIP, WDR5, YEATS2 and ZZZ3 or orthologs. The ATAC complex also regulates the activity of non-histone targets and orchestrates mitotic progression by regulating Cyclin A degradation through acetylation.

The ATAC complex is important because it integrates chromatin acetylation with transcription regulation and cell-cycle progression. Its ability to acetylate both histones and non-histone proteins, including regulation of Cyclin A degradation, places it at a critical node in mitotic control. The complex also represses the autophagy-lysosome pathway via its E3 ubiquitin ligase activity, connecting chromatin regulation to cellular catabolism. Complex-specific inhibitors have been developed to interrogate ATAC histone acetyltransferase complex function, highlighting its potential as a pharmacological target. In disease contexts, epigenetic dysregulation involving chromatin-modifying complexes has been implicated in Alzheimer's disease peripheral immunity, and chromatin accessibility mapping has become a standard approach to study complex diseases [1,3]. Single-cell and spatial multiomic technologies continue to reveal how chromatin regulatory complexes shape cell-type-specific gene expression in human tissues [3,6,7,8].

The ATAC complex is composed of multiple subunits, including HAT module components and additional proteins, each with distinct roles in chromatin regulation and transcription.

The ATAC complex is regulated at the level of subunit composition, as it contains HAT subunits GCN5 or PCAF in a mutually exclusive manner. Complex-specific inhibitors have been developed to interrogate ATAC histone acetyltransferase complex function, providing tools for pharmacological regulation. The ATAC complex also regulates the activity of non-histone targets and orchestrates mitotic progression by regulating Cyclin A degradation through acetylation. Additionally, the ATAC complex represses the transcriptional program of the autophagy-lysosome pathway via its E3 ubiquitin ligase activity, indicating that its functions are integrated with cellular catabolic processes.

Epigenetic dysregulation in Alzheimer's disease peripheral immunity has been described, highlighting the importance of chromatin-modifying complexes in neurodegenerative disease. The ATAC complex, as a chromatin remodeling complex that regulates transcription via acetylation, may contribute to the epigenetic changes observed in Alzheimer's disease. However, direct evidence linking ATAC complex subunits to Alzheimer's disease requires further investigation.

Chromatin accessibility mapping has been applied to study complex diseases, providing insights into regulatory mechanisms. Single-cell atlases of chromatin accessibility in the human genome enable the identification of cell-type-specific regulatory elements that may be influenced by complexes such as ATAC. Mapping enhancer-gene regulatory interactions from single-cell data further connects chromatin accessibility to gene expression in disease contexts.

The ATAC complex represses the transcriptional program of the autophagy-lysosome pathway via its E3 ubiquitin ligase activity. This links the ATAC complex to cellular catabolism and suggests that its dysregulation could impact autophagy-related diseases. Further research is needed to establish causal relationships in human disease.

Single-cell atlases of chromatin accessibility in the human genome provide a method to study how the ATAC complex influences regulatory landscapes. Mapping enhancer-gene regulatory interactions from single-cell data connects chromatin accessibility to gene expression. Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag enables simultaneous measurement of chromatin features.

Spatial multiomic landscape of the human placenta at molecular resolution demonstrates how chromatin regulation can be studied in tissue context. This approach can be adapted to study ATAC complex function in various tissues.

Complex-specific inhibitors for interrogating ATAC histone acetyltransferase complex have been developed, providing tools to dissect its functions. These inhibitors can be used in cell-based assays to study the consequences of ATAC complex inhibition.

The ATAC complex represses the transcriptional program of the autophagy-lysosome pathway via its E3 ubiquitin ligase activity. Transcriptional profiling can be used to identify genes regulated by the ATAC complex. Epigenetic dysregulation in Alzheimer's disease peripheral immunity has been studied using transcriptional approaches.

Researchers studying ATAC complex-related genes often need to determine whether a candidate gene is causally involved in chromatin regulation, transcription, or disease. EDITGENE provides CRISPR-based services to create precise cell models for functional studies of the ATAC complex and its subunits.

The ATAC complex (GO:0140672) is a chromatin remodeling complex that regulates transcription via acetylation of histones H3 and possibly H4, and also regulates non-histone targets and mitotic progression. Its shared HAT module with SAGA and unique subunits distinguish it functionally. The complex represses the autophagy-lysosome pathway via E3 ubiquitin ligase activity, and complex-specific inhibitors enable selective interrogation. Studying the ATAC complex is relevant to understanding chromatin regulation in health and disease, including Alzheimer's disease and complex diseases [1,3]. Researchers can leverage CRISPR-based models and advanced chromatin profiling methods to dissect ATAC complex function [1,3,8]. EDITGENE provides comprehensive services to support these studies.